rs11166983

Variant names:

• chr8-140547987-A-G
• rs11166983
• NM_012154.5:c.1589-360T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012154.5(AGO2):​c.1589-360T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 152,102 control chromosomes in the GnomAD database, including 13,112 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (13112 hom., cov: 32)
• Consequence: AGO2 NM_012154.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110
• Publications: 2 publications found

Genes affected

AGO2 (HGNC:3263): (argonaute RISC catalytic component 2) This gene encodes a member of the Argonaute family of proteins which play a role in RNA interference. The encoded protein is highly basic, and contains a PAZ domain and a PIWI domain. It may interact with dicer1 and play a role in short-interfering-RNA-mediated gene silencing. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

AGO2 Gene-Disease associations (from GenCC):

• Lessel-Kreienkamp syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Illumina, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012154.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGO2	NM_012154.5	MANE Select	c.1589-360T>C		intron	N/A	NP_036286.2
	AGO2	NM_001164623.3		c.1589-360T>C		intron	N/A	NP_001158095.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGO2	ENST00000220592.10	TSL:1 MANE Select	c.1589-360T>C		intron	N/A	ENSP00000220592.5
	AGO2	ENST00000519980.5	TSL:1	c.1589-360T>C		intron	N/A	ENSP00000430176.1
	AGO2	ENST00000523609.5	TSL:1	n.*1174-360T>C		intron	N/A	ENSP00000430164.1

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62289 AN: 151984 Hom.: 13098 Cov.: 32

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.579

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.394

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.410 AC: 62336 AN: 152102 Hom.: 13112 Cov.: 32 AF XY: 0.414 AC XY: 30746 AN XY: 74350

African (AFR) AF: 0.428 AC: 17764 AN: 41498

American (AMR) AF: 0.493 AC: 7530 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1425 AN: 3468

East Asian (EAS) AF: 0.579 AC: 2989 AN: 5160

South Asian (SAS) AF: 0.468 AC: 2255 AN: 4822

European-Finnish (FIN) AF: 0.352 AC: 3728 AN: 10580

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.374 AC: 25453 AN: 67982

Other (OTH) AF: 0.396 AC: 836 AN: 2112

Alfa AF: 0.394 Hom.: 1554

Bravo AF: 0.420

Asia WGS AF: 0.529 AC: 1836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.3
DANN	Benign	0.57
PhyloP100		0.011
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11166983; hg19: chr8-141558086;